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DOVIS 2.0: an efficient and easy to use parallel virtual screening tool based on AutoDock 4.0.

Jiang X, Kumar K, Hu X, Wallqvist A, Reifman J - Chem Cent J (2008)

Bottom Line: We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs.The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability.The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command, Fort Detrick, MD 21702, USA. xjiang@bioanalysis.org

ABSTRACT

Background: Small-molecule docking is an important tool in studying receptor-ligand interactions and in identifying potential drug candidates. Previously, we developed a software tool (DOVIS) to perform large-scale virtual screening of small molecules in parallel on Linux clusters, using AutoDock 3.05 as the docking engine. DOVIS enables the seamless screening of millions of compounds on high-performance computing platforms. In this paper, we report significant advances in the software implementation of DOVIS 2.0, including enhanced screening capability, improved file system efficiency, and extended usability.

Implementation: To keep DOVIS up-to-date, we upgraded the software's docking engine to the more accurate AutoDock 4.0 code. We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs. We also implemented an algorithm to output docked ligands in an industry standard format, sd-file format, which can be easily interfaced with other modeling programs. Finally, we constructed a wrapper-script interface to enable automatic rescoring of docked ligands by arbitrarily selected third-party scoring programs.

Conclusion: The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability. The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands. The new DOVIS 2.0 package is freely available to the public under the GNU General Public License.

No MeSH data available.


Superimpositions of the X-ray ligand and docked ligand poses to the 1STPand 1RBPcomplexes. The X-ray ligand is shown in green; the docked ligand using the all-atom model is shown in orange; and the docked ligand position derived from the polar-hydrogen model is shown in cyan, where the non-polar hydrogens were artificially added in the representation.
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Figure 2: Superimpositions of the X-ray ligand and docked ligand poses to the 1STPand 1RBPcomplexes. The X-ray ligand is shown in green; the docked ligand using the all-atom model is shown in orange; and the docked ligand position derived from the polar-hydrogen model is shown in cyan, where the non-polar hydrogens were artificially added in the representation.

Mentions: Table 1 lists the RMSD values and associated AutoDock 4.0 scores of the docked ligand poses with the lowest RMSD for each of the eight complexes. The RMSD values of the all-atom model and of the polar-hydrogen model are similar for all eight complexes. For all complexes, except 4DFR (RMSD > 5.00 Å), the program found ligand poses close to the experimentally determined ligand pose. Table 1 also indicates that, except for 1RBP, where the score of the all-atom model is much lower (predicting less binding affinity) than the score of the polar-hydrogen model, both models produce similar scores. Figure 2 shows the X-ray ligand and the docked ligand poses from the complexes of 1STP and 1RBP. In the case of 1RBP, we believe that van der Waals (vdW) clashes between the receptor and ligand atoms in the all-atom model caused the difference between the two scores, because, as shown in Figure 2, the binding site of 1RBP is very cramped. In fact, the vdW radii in AutoDock 4.0 were enlarged to compensate for missing non-polar hydrogens. Although our tests suggest that the docking results of both models are generally similar, even when the provided default parameters are used, users should be cautious about using the all-atom model with the default parameters. For a more accurate representation, users should scale down the vdW radii and re-parameterize the AutoDock 4.0 scoring function when applying the all-atom model.


DOVIS 2.0: an efficient and easy to use parallel virtual screening tool based on AutoDock 4.0.

Jiang X, Kumar K, Hu X, Wallqvist A, Reifman J - Chem Cent J (2008)

Superimpositions of the X-ray ligand and docked ligand poses to the 1STPand 1RBPcomplexes. The X-ray ligand is shown in green; the docked ligand using the all-atom model is shown in orange; and the docked ligand position derived from the polar-hydrogen model is shown in cyan, where the non-polar hydrogens were artificially added in the representation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2542995&req=5

Figure 2: Superimpositions of the X-ray ligand and docked ligand poses to the 1STPand 1RBPcomplexes. The X-ray ligand is shown in green; the docked ligand using the all-atom model is shown in orange; and the docked ligand position derived from the polar-hydrogen model is shown in cyan, where the non-polar hydrogens were artificially added in the representation.
Mentions: Table 1 lists the RMSD values and associated AutoDock 4.0 scores of the docked ligand poses with the lowest RMSD for each of the eight complexes. The RMSD values of the all-atom model and of the polar-hydrogen model are similar for all eight complexes. For all complexes, except 4DFR (RMSD > 5.00 Å), the program found ligand poses close to the experimentally determined ligand pose. Table 1 also indicates that, except for 1RBP, where the score of the all-atom model is much lower (predicting less binding affinity) than the score of the polar-hydrogen model, both models produce similar scores. Figure 2 shows the X-ray ligand and the docked ligand poses from the complexes of 1STP and 1RBP. In the case of 1RBP, we believe that van der Waals (vdW) clashes between the receptor and ligand atoms in the all-atom model caused the difference between the two scores, because, as shown in Figure 2, the binding site of 1RBP is very cramped. In fact, the vdW radii in AutoDock 4.0 were enlarged to compensate for missing non-polar hydrogens. Although our tests suggest that the docking results of both models are generally similar, even when the provided default parameters are used, users should be cautious about using the all-atom model with the default parameters. For a more accurate representation, users should scale down the vdW radii and re-parameterize the AutoDock 4.0 scoring function when applying the all-atom model.

Bottom Line: We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs.The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability.The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands.

View Article: PubMed Central - HTML - PubMed

Affiliation: Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command, Fort Detrick, MD 21702, USA. xjiang@bioanalysis.org

ABSTRACT

Background: Small-molecule docking is an important tool in studying receptor-ligand interactions and in identifying potential drug candidates. Previously, we developed a software tool (DOVIS) to perform large-scale virtual screening of small molecules in parallel on Linux clusters, using AutoDock 3.05 as the docking engine. DOVIS enables the seamless screening of millions of compounds on high-performance computing platforms. In this paper, we report significant advances in the software implementation of DOVIS 2.0, including enhanced screening capability, improved file system efficiency, and extended usability.

Implementation: To keep DOVIS up-to-date, we upgraded the software's docking engine to the more accurate AutoDock 4.0 code. We developed a new parallelization scheme to improve runtime efficiency and modified the AutoDock code to reduce excessive file operations during large-scale virtual screening jobs. We also implemented an algorithm to output docked ligands in an industry standard format, sd-file format, which can be easily interfaced with other modeling programs. Finally, we constructed a wrapper-script interface to enable automatic rescoring of docked ligands by arbitrarily selected third-party scoring programs.

Conclusion: The significance of the new DOVIS 2.0 software compared with the previous version lies in its improved performance and usability. The new version makes the computation highly efficient by automating load balancing, significantly reducing excessive file operations by more than 95%, providing outputs that conform to industry standard sd-file format, and providing a general wrapper-script interface for rescoring of docked ligands. The new DOVIS 2.0 package is freely available to the public under the GNU General Public License.

No MeSH data available.